Our laboratory is studying the regulatory aspects of glycogen metabolism. We are investigating and refining the 2.1 A resolution structure of rabbit muscle glycogen phosphorylase using x-ray diffraction. We are improving the atomic model and study by difference Fourier and model building, the effects on the enzyme's structure by the binding of various ligands that effect glycogen metabolism and glucose homeostasis in vivo. These ligands include oligosaccharides, AMP, G-1-P, G-6-P, ATP, glucose, UDPG, F-1-P, Pi and purine analogs. We are doing experiments in order to understand the link between the purine inhibitor binding site on phosphorylase and glucose homeostasis. We are trying to identify a previously unrecognized in vivo land using HPLC, mass spectrometry, cell kinetics and x-ray diffraction. A second aspect of this problem is to understand the molecular basis of regulation of glycogen metabolism by the ligand induced T/R conformational switch. We are trying to solve the x-ray structure of R conformation enzyme which we shall compare with the structure we already have for the T conformation enzyme. This should show the two principal conformational states of the enzyme in vivo and help determine the molecular basis of hormone induced (Ser 14-phosphorylation) and ligand effect enzyme regulation.